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Biomedical subjects

S Ohno

Publications and source records attributed to S Ohno.

At least 361 records · Page 20Linked to original sources
PubMed1997

Genetic influences on sarcoidosis.

To investigate the genetic influences underlying the development of sarcoidosis, HLA class II genotyping was performed in Japanese patients with sarcoidosis and healthy controls using the PCR-RFLP method. The frequencies of both DR52 group antigen-associated alleles (HLA-DRB1*11, -DRB1*12 and -DRB1*14) and DRB1*08 alleles were higher in the patient group, suggesting that the common, specific amino acid residue on the DRB1 molecule of these alleles may determine susceptibility to sarcoidosis. Alternatively, it is possible that another susceptibility gene, linked to these DRB1 alleles, exists within the MHC region. We screened the TNFA, TNFB, HSP70-1 and Hum70t genes around the class III region, as well as the HLA-DMA and -DMB genes in the class II region, for genetic polymorphism in sarcoidosis. None of these genes suggested a susceptibility to sarcoidosis. These studies support the thesis that one of the major genetic factors controlling the development of sarcoidosis is located within the DRB1 locus in the HLA class II region.

Cytokines↗
PubMed1997

An immunocytochemical study of changes in the human erythrocyte membrane skeleton produced by stretching examined by the quick-freezing and deep-etching method.

A quick-freezing and deep-etching method in combination with erythrocyte splitting was used to examine the cytoplasmic aspect of whole-mount human erythrocyte membranes. Various external forces induced alterations in membrane skeletal organisation during the splitting procedure. The initial change was elongation in the peripheral part of the membrane skeleton, examined by immunostaining with a monoclonal antispectrin antibody. Under severe stretching conditions, a linear rearrangement of filamentous components was evident; these were disposed parallel to the rim of the erythrocyte, while the central part of the concavity exhibited a more compacted structure. These changes resulted in a different distribution of membrane skeletal components between central rigid and peripheral flexible areas in biconcave erythrocytes. It is suggested that the reversible membrane skeletal changes in the flexible areas which resist the external forces are important for maintaining the normal framework of biconcave human erythrocytes.

Antibodies, Monoclonal↗
PubMed1997

Electron microscopic study of erythroblastic islands obtained by 'tissue-stamp culture' method.

A new 'tissue-stamp culture' method was developed for stamping proliferating erythroblasts of mouse spleens on collagen-coated coverslips after inducing haemolytic anaemia by administration of 1-acetyl-2-phenylhydrazine, and then adherent splenic cells were cultured for a few days. We could obtain many erythroblastic islands, where cultured erythroblasts were located over macrophages and were proliferated synchronously for 10-30 h, and then the erythroblasts were differentiated and enucleated after 30-50 h in the presence of erythropoietin. To observe three-dimensional structures of the erythroblastic islands, a scanning electron microscope was used for the cultured cells treated with critical point-drying method. Immature wrinkled erythroblasts with many micropinocytic pits were attached to the central area of the flattened macrophages with many cytoplasmic projections, though matured erythroblasts were localized on their peripheral areas. Moreover, cytoplasmic projections of underlying macrophages, which were attached to the matured erythroblasts, were decreased in number. At a late stage, deep cytoplasmic invaginations of erythroblasts observed at a middle stage became shallow after their enucleation and flattened to form their concave shapes. This 'tissue-stamp culture' system would be useful for studying specific interaction between stromal macrophages and haematopoietic cells.

Anemia, Hemolytic↗
PubMed1997

Analysis of allelic variation of the TAP2 gene in sarcoidosis.

Sarcoidosis is a systemic granulomatous disease and the DRB1 gene of the DR subregion has been implicated for determining the genetic susceptibility to the disease. We evaluated the allelic variation of the TAP2 gene using the PCR-RFLP method as well as the mismatched PCR-RFLP method in 82 Japanese patients with sarcoidosis and 92 healthy controls. A new allele, TAP2*0103 and a new polymorphic variation at codon 577 in addition to TAP2*0101, TAP2*0102 and TAP2*0201 have been recognized in the Japanese subjects. No significant differences were observed in the frequencies of any TAP2 alleles or dimorphism at codon 577 between the patients and healthy controls. Polymorphic variation of the TAP2 gene does not confer the susceptibility to sarcoidosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Immunogenetic study of sympathetic ophthalmia.

Sympathetic ophthalmia (SO) is very rare but it remains one of the most intractable eye diseases. In clinical manifestations and histopathologic features SO is known to resemble closely Vogt-Koyanagi-Harada's disease (VKH disease). We had reported that VKH disease was significantly associated with HLA-DRB1*04 and -DQB1*04 in Japanese patients. In this study, to investigate an HLA association with SO we performed HLA serological and PCR-based DNA typing in 16 patients and 50 healthy controls. Our study revealed that HLA-DRB1*04 (0405; Pc < 5 x 10(-4)), DQA1*03 (Pc < 5 x 10(-3)), and DQB1*04 (0401; Pc < 5 x 10(-4)) were significantly associated with SO as compared to the healthy controls but there was no significant difference in the frequencies of any DPB1 alleles between the patients and healthy controls. It can be postulated that not only the clinical manifestations but also the genetic predisposition of SO are very similar to those of VKH disease.

Female↗
PubMed1997

MICA gene and ankylosing spondylitis: linkage analysis via a transmembrane-encoded triplet repeat polymorphism.

In order to address the possibility that the MICA gene located 47 kb upstream from HLA-B is involved in the pathogenesis of ankylosing spondylitis (AS), we have investigated microsatellite polymorphism in the transmembrane region of MICA in Caucasian patients with AS. The microsatellite allele consisting of 4 repetitions of GCT/AGC was present at significantly higher frequency in the patient group (Pc<0.0000001) than in the ethnically matched control group. However, the frequency of the (GCT/AGC)4 allele was significantly low in the B27-positive patients than in the B27-positive healthy controls (Pc=0.0145). These observations suggest that B27 itself remains the primary genetic marker for AS, although the significantly dissimilar phenotype frequency of the (GCT/AGC)4 allele in B27-positive patients and healthy individuals may reflect the existence of other genetic factor(s) in the HLA-B27 haplotype involved in the development of AS.

Alleles↗
PubMed1997

Identification of a novel HLA-B allele (B*4202) in a Saudi Arabian family with Behçet's disease.

A new HLA-B antigen, tentatively called HLA-B42AND, was identified as a B42 serologic variant in a Saudi Arabian family. DNA sequencing analysis of the second and third exon of this new B allele revealed that B42AND was identical to B*4201 except for a single T to C substitution at position 97 of exon 2. This substitution results in histidine (CAC) at codon 9 in B42AND instead of tyrosine (TAC) in B*4201. The antigen frequency of B42AND in a Saudi Arabian population was around 10%. This novel B42AND has officially been named HLA-B*4202.

Alleles↗
PubMed1997

A strong association between HLA-B*5101 and Behçet's disease in Greek patients.

Behçet's disease is known to be associated with HLA-B51, one of the split antigens of HLA-B5, among many different ethnic groups. In a Greek population, an increased incidence of HLA-B5 in the patient group has also been reported. Because the B51 antigen has been recently identified to comprise seven alleles, B*5101-B*5107, we performed HLA-B51 allele genotyping by the PCR-SSP method as well as serological HLA-A and -B typing among 31 Greek patients with Behçet's disease to investigate whether there is any correlation between one particular B51-associated allele and Behçet's disease. The frequency of B51 was remarkably high (80.6%) in the patient group as compared to the ethnically matched control group (26.7%). In addition, HLA-A26 was also increased in the patients (29.0%) as compared with the healthy controls (3.3%). B51 allele genotyping revealed that all these B51-positive patients carried B*5101. This study revealed a strong association of Behçet's disease in Greeks with one of the B51 subantigens, providing insight into the molecular mechanism underlying an HLA association with Behçet's disease.

Behcet Syndrome↗
PubMed1997

Major histocompatibility complex class II alleles in Kazak and Han populations in the Silk Route of northwestern China.

Genetic polymorphism of the HLA class II loci including the DRB1, DQA1, DQB1 and DPB1 genes was investigated by the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method in a Kazak population inhabiting the most northwestern part of China, Urümqi in the Xinjiang Uygur Zizhiqu as well as in a Han population in the same area. Forty-two Kazak and 59 Han unrelated volunteers were enrolled in this study. Among 51 DRB1 alleles tested, 29 alleles were detected, and DRB1*0301 (13.1%) and DRB1*07 (10.7%) in Kazak and DRB1*0901 (11.9%), DRB1*1501 (11.0%) and DRB1*07 (11.0%) in northwestern Han were highly predominant. In 8 DQA1 alleles detected, DQA1*0501 (29.8%) and DQA1*0301 (23.8%) in Kazak, and DQA1*0301 (28.8%) and DQA1*0102 (19.5%) in northwestern Han were the most and the second most common alleles, respectively. Of 18 DQB1 alleles tested, 14 were observed, among which DQB1*0201 and DQB1*0301 were very frequent both in Kazak (23.8% and 21.4%, respectively) and northwestern Han (18.6% and 16.9%, respectively) populations. Of 37 DPB1 alleles tested, 14 were detected. Among them, the frequencies of DPB1*0401 (21.4%), DPB1*0501 (20.2%), DPB1*0402 (19.0%) and DPB1*0201 (16.7%) in Kazak, and those of DPB1*0501 (38.1%) and DPB1*0201 (16.1%) in northwestern Han were highly increased. Several three-locus haplotypes were recognized to predominate significantly, namely DRB1*0301-DQA1*0501-DQB1*0201 (13.1%) and DRB1*0701-DQA1*0201-DQB1*0201 (8.3%) in Kazak; and DRB1*0901-DQA1*0301-DQB1*0303 (11.9%) and DRB1*0701-DQA1*0201-DQB1*0201 (10.2%) in northwestern Han. The dendrogram constructed by the neighbor-joining (NJ) method based on the allele frequencies of the DRB1, DQA1, DQB1 and DPB1 genes of 12 representative populations all over the world including northern Han, southern Han, Manchu and Japanese suggested that Kazak and northwestern Han were the closest to each other, but Kazak was a little farther from the Asian ethnic groups than northwestern Han.

Alleles↗
PubMed1997

Genetic polymorphism in intron 6 of the LMP7 gene in Japanese and its association with sarcoidosis.

Genetic polymorphism in intron 6 of the LMP7 gene was investigated using polymerase chain reaction-restriction fragment length polymorphism in 90 unrelated healthy Japanese controls and 66 Japanese patients with sarcoidosis. Four alleles, including two new ones recently identified in Koreans, LMP7*C and LMP7*D, were found in the Japanese population. The frequency of LMP7*C in the sarcoidosis patients was higher than in the healthy controls. However, this difference might be explained by a secondary association with HLA-DRB1*08 in the HLA-DRB1 gene, which is thought to be the gene primarily responsible for susceptibility to sarcoidosis.

Alleles↗
PubMed1997

Tumor promotion by depleting cells of protein kinase C delta.

Tumor-promoting phorbol esters activate, but then deplete cells of, protein kinase C (PKC) with prolonged treatment. It is not known whether phorbol ester-induced tumor promotion is due to activation or depletion of PKC. In rat fibroblasts overexpressing the c-Src proto-oncogene, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced anchorage-independent growth and other transformation-related phenotypes. The appearance of transformed phenotypes induced by TPA in these cells correlated not with activation but rather with depletion of expressed PKC isoforms. Consistent with this observation, PKC inhibitors also induced transformed phenotypes in c-Src-overexpressing cells. Bryostatin 1, which inhibited the TPA-induced down-regulation of the PKCdelta isoform specifically, blocked the tumor-promoting effects of TPA, implicating PKCdelta as the target of the tumor-promoting phorbol esters. Consistent with this hypothesis, expression of a dominant negative PKCdelta mutant in cells expressing c-Src caused transformation of these cells, and rottlerin, a protein kinase inhibitor with specificity for PKCdelta, like TPA, caused transformation of c-Src-overexpressing cells. These data suggest that the tumor-promoting effect of phorbol esters is due to depletion of PKCdelta, which has an apparent tumor suppressor function.

Animals↗
PubMed1997

Ultrastructural study of glomerular capillary loops at different perfusion pressures as revealed by quick-freezing, freeze-substitution and conventional fixation methods.

Wistar rat kidneys were perfused with some fixatives at different pressures of 100, 150, 200 or 250 cm H2O via the aorta and were studied by the quick-freezing and freeze-substitution (QF-FS) or deep-etching (QF-DE) methods, in addition to the conventional immersion or perfusion fixation method. Different parts of glomerular capillary walls were selected for morphometric analyses. It was demonstrated that the widths of glomerular slit diaphragms and the spaces between foot processes were more widely dilated at higher perfusion pressures (200 and 250 cm H2O) than those seen at both normal perfusion pressure (150 cm H2O) and lower perfusion pressure (100 cm H2O). On the other hand, the glomerular basement membranes were thinner at higher perfusion pressures. By the QF-FS and QF-DE methods, the foot processes showed different shapes from those revealed by the conventional preparation methods, even at the same perfusion pressure. It is concluded that the widths of glomerular slit diaphragms and glomerular basement membranes and the spaces between foot processes may be significantly changed in vivo, depending on the hemodynamics in the glomerular capillary.

Animals↗
PubMed1997

Ultrastructural study of axonal cytoskeletons in the optic nerve damaged by acutely elevated intraocular pressure using the quick-freezing and deep-etching technique.

The aim of this study was to examine the ultrastructure of axonal cytoskeletons in guinea pig optic nerve damage induced by acutely elevated intraocular pressure (IOP) employing the quick-freezing and deep-etching method. An IOP of 60 mm Hg was maintained for 4 h. The unmyelinated axoplasm of the optic nerve at the normal IOP was filled with longitudinally oriented neurofilaments and bundled microtubules, which were cross-linked by numerous cross-bridges. Membranous organelles, such as mitochondria and vesicles, were scattered in the axoplasm. These organelles were similarly interconnected with microtubules or neurofilaments by the cross-bridges. The unmyelinated axoplasm of the optic nerve following acutely elevated IOP was shown to include intraaxonal collections of various membranous organelles and reduction of microtubules and neurofilaments. The cross-bridges linking microtubules, neurofilaments and membranous organelles in such axoplasm appeared to be dramatically reduced in number. Thus, it is suggested that the ultrastructural changes of axonal cytoskeletons in some optic nerves following elevated IOP might include the reduction of microtubules, neurofilaments and their associated cross-bridges.

Animals↗
PubMed1997

The seroprevalence of HTLV-I in patients with ocular diseases, pregnant women and healthy volunteers in the Kanto district, central Japan.

HTLV-I has been shown to be related to the development of inflammatory diseases in various organs such as the eyes, lungs and joints. In south-west Japan where HTLV-I is highly endemic, the term 'HTLV-I associated complex' has been approved. To investigate the seroprevalence of HTLV-I in the Kanto district in central Japan, we have estimated the frequency of seropositivity to HTLV-I in 2,110 patients with various ocular diseases and 2,683 pregnant women, in addition to 5,336 healthy volunteers. Of the healthy volunteers, only 42 (0.79%) were seropositive, and the HTLV-I seroprevalence in pregnant women was also only 16/2,683 (0.60%) which was almost equal to that in female healthy volunteers aged 15-44 years (0.59%). In patients with various ocular diseases, however, there was significantly higher seroprevalence of HTLV-I (2.32%) compared with healthy volunteers in each sex (male: p = 0.0029; female: p = 0.000023). These results suggest that the seroprevalence of HTLV-I in the Kanto district is much lower than in south-west Japan. On the other hand, HTLV-I infection was shown to be correlated to ocular diseases also in the Kanto district. In particular, we found a higher seroprevalence of HTLV-I in patients with inflammatory ocular disease, such as endogenous uveitis, episcleritis, retinitis pigmentosa and degenerative choroiditis. This possibly suggests a causative role of HTLV-I in the development of these inflammatory ocular diseases also where HTLV-I is not endemic.

Adolescent↗
PubMed1997

Pathogenic gene responsible for the predisposition of Behçet's disease.

HLA-B51 is well known to be associated with Behçet's disease (BD) in many different ethnic groups. The hypothesis may be presented that B51 molecules are primarily involved in BD development through specific antigen presentation. Furthermore, HLA-C genotyping by the polymerase chain reaction-sequence specific primers method suggests that the BD pathogenic gene is not the HLA-C gene itself but some other gene located near the HLA-B gene. Polymorphic analysis of the Tau-a microsatellite between the HLA-B and TNF genes indicates that the pathogenic gene of BD is not the HLA-B51 gene itself but other gene located around the HLA-B gene. Recent studies suggest that many novel genes exist in the region between the TNF and HLA-B or HLA-C genes such as MIC and PERB, etc. and furthermore, many unidentified new genes have been suggested to exist in this region. In this paper, the present situation of the investigations on the genetic predisposition responsible for BD was reviewed.

Animals↗
PubMed1997

Molecular genetics (HLA) of Behçet's disease.

Behçet's disease (BD) has been known to be strongly associated with the human leukocyte antigen (HLA) B51. This B51 association has been confirmed in many different ethnic groups between the Middle East and Japan, and it has been proposed that BD is prevalent in those ethnic groups along the old Silk Route. The hypothesis could be made that B51 molecules are primarily involved in BD development through specific antigen presentation. However, polymorphic analyses of the TNFB gene and Tau-a microsatellite between the HLA-B and TNF genes indicate that the pathogenic gene of BD is not the HLA-B51 gene itself but another gene located around the HLA-B gene. HLA-C genotyping by the PCR-SSP method also suggests that the BD pathogenic gene is not the HLA-C gene itself but other gene located near the HLA-B gene. Recently we sequenced a single contig of 236,822 bp from the MICA gene (58.2 kb centromeric of HLA-B) to 90.8 kb telomeric of HLA-C and identified 8 novel genes designated NOB1-8 (NOB: new organization associated with HLA-B). During the course of the genomic sequence analysis we clarified the genetic structure of the MICA (MHC class I chain-related gene A) gene and found a triplet repeat microsatellite polymorphism of (GCT/AGC)n in the transmebrane (TM) region. Furthermore, the microsatellite allele consisting of 6 repetitions of GCT/AGC (MICA A6 allele) was present at a significantly higher frequency in the BD patient group than in the control group and a significant fraction of B51-negative patients were positive for this MICA A6 allele. These results suggest the possibility of a primary association of BD with MICA rather than HLA-B.

Animals↗